DNA G-Quadruplexes Contribute to CTCF Recruitment
| Autor: | A.N. Bogomazova, Artem V. Luzhin, Galina E. Pozmogova, Maria A. Lagarkova, Omar L. Kantidze, Vjacheslav V. Severov, Anna Varizhuk, Tatjana Vedekhina, Polina Tikhonova, Ekaterina Isaakova, R. Sultanov, Ksenia Klimina, Vladimir B. Tsvetkov, Iulia I. Pavlova |
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| Rok vydání: | 2021 |
| Předmět: |
CCCTC-Binding Factor
QH301-705.5 Biology Article Catalysis Chromatin remodeling chromatin remodeling Inorganic Chemistry 03 medical and health sciences HMG proteins 0302 clinical medicine Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy 030304 developmental biology Genetics 0303 health sciences G-quadruplex Genome Human Organic Chemistry General Medicine DNA Methylation Hmg protein CTCF Chromatin Computer Science Applications G-Quadruplexes Chemistry High-mobility group CpG site CpG methylation DNA methylation CpG Islands Human genome K562 Cells 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 13 International Journal of Molecular Sciences, Vol 22, Iss 7090, p 7090 (2021) |
| ISSN: | 1422-0067 |
| Popis: | G-quadruplex (G4) sites in the human genome frequently colocalize with CCCTC-binding factor (CTCF)-bound sites in CpG islands (CGIs). We aimed to clarify the role of G4s in CTCF positioning. Molecular modeling data suggested direct interactions, so we performed in vitro binding assays with quadruplex-forming sequences from CGIs in the human genome. G4s bound CTCF with Kd values similar to that of the control duplex, while respective i-motifs exhibited no affinity for CTCF. Using ChIP-qPCR assays, we showed that G4-stabilizing ligands enhance CTCF occupancy at a G4-prone site in STAT3 gene. In view of the reportedly increased CTCF affinity for hypomethylated DNA, we next questioned whether G4s also facilitate CTCF recruitment to CGIs via protecting CpG sites from methylation. Bioinformatics analysis of previously published data argued against such a possibility. Finally, we questioned whether G4s facilitate CTCF recruitment by affecting chromatin structure. We showed that three architectural chromatin proteins of the high mobility group colocalize with G4s in the genome and recognize parallel-stranded or mixed-topology G4s in vitro. One of such proteins, HMGN3, contributes to the association between G4s and CTCF according to our bioinformatics analysis. These findings support both direct and indirect roles of G4s in CTCF recruitment. |
| Databáze: | OpenAIRE |
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